Making Old Stem Cells Functionally Young

More rejuvenation of stem cell function demonstrated in mice: "Researchers have rejuvenated aged hematopoietic stem cells to be functionally younger, offering intriguing clues into how medicine might one day fend off some ailments of old age. ... The paper brings new perspective to what has been a life science controversy - countering what used to be broad consensus that the aging of hematopoietic stem cells (HSCs) was locked in by nature and not reversible by therapeutic intervention. HSCs are stem cells that originate in the bone marrow and generate all of the body's red and white blood cells and platelets. They are an essential support mechanism of blood cells and the immune system. As humans and other species age, HSCs become more numerous but less effective at regenerating blood cells and immune cells. ... Researchers in the current study determined a protein that regulates cell signaling - Cdc42 - also controls a molecular process that causes HSCs from mice to age. Pharmacologic inhibition of Cdc42 reversed HSC aging and restored function similar to that of younger stem cells. ... We know the aging of HSCs reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia, and may be the cause of tissue attrition in certain systems of the body. ... One reason the research team focused on Cdc42 is that previous studies have reported elevated activity of the protein in various tissue types of older mice - which have a natural life span of around two years. Also, elevated expression of Cdc42 has been found in immune system white blood cells in older humans. In the current study, researchers found elevated activity of Cdc42 in the HSCs of older mice. They also were able to induce premature aging of HSCs in mice by genetically increasing Cdc42 activity in the cells. ... To test the rejuvenated cells, the researchers used a process known as serial competitive transplantation. This included extracting HSCs from young (2-4 months) and aged (20-26 months) mice and processing them in laboratory cultures. Young and rejuvenated cells were then engrafted into recipient mice. This allowed scientists to compare how well young and rejuvenated aged HSCs started to repopulate and transform into different types of blood cells. It also confirmed that HSCs rejuvenated by targeting Cdc42 do function similarly to young stem cells."



If my analysis of the literature is correct, CDC42 expression increases the propensity of cells to lose their "stemness" and more apt to continue their differentiation program toward senescence.

CDC42 expression appears to increase with age in most tissues, and also seems to be the gene most predictive of future mortality rate. See -
"Gene expression profiles associated with aging and mortality in humans";jsessionid=RVtAgStwUPBzKfgafOVc.8?pdf=render

BTW, the morphology of aged cells can be rolled back to a more youthful stage by a related down-stream pathway - RNAi knockout of caveolin-1 expression -
"Morphological Adjustment of Senescent Cells by Modulating Caveolin-1 Status"

Posted by: Lou Pagnucco at May 6th, 2012 9:38 AM
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